Burkart, Kristin M., Sofer, Tamar, London, Stephanie J., Manichaikul, Ani, Hartwig, Fernando P., Yan, Qi, Artigas, María Soler, Avila, Lydiana, Chen, Wei, Thomas, Sonia Davis, Diaz, Alejandro A., Hall, Ian P., Horta, Bernardo L., Kaplan, Robert C., Laurie, Cathy C., Menezes, Ana M., Morrison, Jean V., Oelsner, Elizabeth C., Rastogi, Deepa, Rich, Stephen S., Soto-Quiros, Manuel, Stilp, Adrienne M., Tobin, Martin D., Wain, Louise V., Celedon, Juan C. and Barr, R. Graham
(2018)
A genome-wide association study in Hispanics/Latinos identifies novel signals for lung function: the Hispanic Community Health Study/Study of Latinos.
American Journal of Respiratory and Critical Care Medicine
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ISSN 1535-4970
Full text not available from this repository.
Abstract
Rationale:: Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.
Objectives: Perform a GWAS of COPD-phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.
Methods: :GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies.
Measurements and Main Results: Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for forced expiratory volume in one second (FEV1) in ZSWIM7 (rs4791658; p=4.99×10-9) replicated. A rare variant (MAF=0.002) in HAL (rs145174011) was associated with FEV1 to forced vital capacity (FEV1/FVC) (p=9.59×10-9) in a region previously identified for COPD-related phenotypes; it remained significant in conditional analyses but did not replicate. Admixture mapping identified a novel region, with a variant in AGMO (rs41331850), associated with Amerindian ancestry and FEV1, which replicated. A novel locus for FEV1 identified among ever smokers (rs291231; p=1.92×10-8) approached statistical significance for replication in admixed populations of African ancestry and a novel SNP for COPD in PDZD2 (rs7709630; p=1.56×10-8) regionally replicated. Additionally, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in HCHS/SOL at the genome-wide significance level.
Conclusions: We identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing togenetic etiologies of COPD.
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